rs10482605

Positions:

• chr5-143403956-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364183.2(NR3C1):​c.-13-3104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 984,588 control chromosomes in the GnomAD database, including 12,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1513 hom., cov: 32)
  • Exomes 𝑓: 0.16 (11220 hom.)
• Consequence: NR3C1 NM_001364183.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

Genes affected

NR3C1 (HGNC:7978): (nuclear receptor subfamily 3 group C member 1) This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011]

NR3C1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR3C1	NM_001364183.2	c.-13-3104T>C		intron_variant			NP_001351112.1
NR3C1	NM_001364184.2	c.-14+420T>C		intron_variant			NP_001351113.1
NR3C1	NM_001018074.1	c.-13-3104T>C		intron_variant			NP_001018084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR3C1	ENST00000504572.5	c.-13-3104T>C		intron_variant		1		ENSP00000422518.1
NR3C1	ENST00000503201.1	c.-14+420T>C		intron_variant		1		ENSP00000427672.1
NR3C1	ENST00000502892.5	c.-14+663T>C		intron_variant		1		ENSP00000420856.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19849 AN: 151088 Hom.: 1519 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.163 AC: 135713 AN: 833390 Hom.: 11220 Cov.: 32 AF XY: 0.164 AC XY: 62975 AN XY: 384918

Gnomad4 AFR exome AF: 0.0896

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.00110

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.131 AC: 19836 AN: 151198 Hom.: 1513 Cov.: 32 AF XY: 0.127 AC XY: 9390 AN XY: 73886

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.155

Alfa AF: 0.144 Hom.: 223

Bravo AF: 0.131

Asia WGS AF: 0.0750 AC: 260 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10482605; hg19: chr5-142783521;